NEURAL CONTROL OF LACRIMAL GLAND SECRETION

泪腺分泌的神经控制

• 批准号: 2391729
• 负责人: BENJAMIN WALCOTT
• 金额: $ 28.71万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-01-01 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2391729
• 关键词: Sjogren's syndrome; acinar cell; biological signal transduction; calcium channel; carbachol; chickens; cyclic AMP; enzyme linked immunosorbent assay; excitatory aminoacid; immunocytochemistry; immunoglobulin A; immunoglobulin G; immunoglobulins; innervation; laboratory mouse; lacrimal apparatus; membrane channels; neurotransmitters; plaque assay; plasma cells; potassium channel; receptor binding; secretion; tear; voltage /patch clamp

Dry eye is a painful, debilitating and often serious condition that is observed particularly in older women. It is characterized by an inability of the tear glands to produce sufficient tear fluid to wet the ocular surface and often results in inflammation and damage to the cornea and conjunctiva. At best, the condition is painful and requires the regular use of eye drops and at worst, if untreated, it can result in significant loss of visual acuity due to damage to the cornea. There are a number of different disease conditions that can cause the lacrimal glands to reduce or stop their secretion but one of the most common and well characterized is Sjorgen's syndrome. In this disease, the lacrimal glands (and salivary glands as well) become infiltrated with large numbers of lymphocytes from the immune system that destroy portions of the lacrimal gland tissue yet the remaining apparently normal appearing tissue is unable to function. The basic question, then, is why doesn't the rest of the gland continue to function. The MRL and NZB strains of mice are useful models of the disease condition and will be used along with normal mice in anatomical and physiological studies to determine what processes in the stimulus-secretion pathway have been affected by the disease.Immunocytochemistry will be used to detail the normal pattern of innervation of the lacrimal glands and to determine the neurotransmitters present. Examination of diseased glands from the MRL and NZB mice will determine what effects the infiltration has on the innervation. Experiments using isolated glands from normal and diseased animals will show whether secretion can be induced by the exposure of the tissue to known excitatory neurotransmitters and other stimulatory agents. Finally, cells will be isolated from normal and diseased glands and patch-clamp techniques will be used to characterize the ion channels present on the surface membranes of the secretory cells and to determine the changes that occur in the disease states. Such ion channels are important in the fluid transport process of the gland and are a reliable measure of its activity. These studies, therefore, will determine at what point(s) ina the stimulus-secretion process the disease process of Sjogren's syndrome is breaking the link and will assist in the process of finding a treatment to ameliorate the symptoms at least while normal tissue is still present.

干眼是一种痛苦，令人衰弱的，通常是严重的状况 特别是在老年妇女中观察到。 它的特征是无法 泪腺产生足够的泪液以润湿眼部 表面并经常会导致炎症和角膜的损害 结膜。 充其量，病情很痛苦，需要常规 使用眼滴，在最坏的情况下，如果未经治疗，它可能会导致大量 由于对角膜的损害，视力丧失。 有很多 不同的疾病状况，可能导致泪腺减少 或停止他们的分泌，但最常见和特征是 是Sjorgen综合征。 在这种疾病中，泪腺（和唾液 腺体也被大量的淋巴细胞浸润 破坏泪腺组织部分的免疫系统 其余的显然正常出现的组织无法发挥作用。 那么，基本问题是为什么其余的腺体不继续 功能。 小鼠的MRL和NZB菌株是该疾病的有用模型 条件并将与正常小鼠一起在解剖学中使用 生理研究以确定刺激分泌过程中的哪些过程 途径已受到疾病的影响。将使用免疫细胞化学 详细说明泪腺神经支配的正常模式和至 确定存在的神经递质。 检查患病的腺体 从MRL和NZB小鼠中，将确定渗透的影响 在神经上。 实验使用正常和 患病的动物将表明是否可以通过暴露诱导分泌物 组织到已知的兴奋性神经递质和其他刺激性的 代理商。 最后，将从正常和患病的腺体中分离出细胞 和贴片钳技术将用于表征离子通道 存在于分泌细胞的表面膜上，并确定 疾病状态发生的变化。 这样的离子通道是 在腺体的流体传输过程中很重要，并且是可靠的 衡量其活性。 因此，这些研究将决定什么 点（s）刺激 - 分泌过程疾病过程 Sjogren综合征正在打破链接，并将在 至少在正常组织时找到一种治疗方法以改善症状 仍然存在。